Abstract Patients with hormone receptor–positive (HR+) inflammatory breast cancer (IBC) who have residual disease after surgery represent a particularly high-risk group, yet current adjuvant treatment guidelines do not address their elevated recurrence rates compared with non-inflammatory breast cancers. In this single-center phase II study, 31 such patients (enrolled 2017–2021) received pembrolizumab every three weeks for up to 24 months combined with standard endocrine therapy. The median number of doses administered was 19, and 8 patients (26%) completed the full course of treatment. Two-year disease-free survival was 71% (95% CI, 57–89%), and median overall survival was not reached (median follow-up, 48 months). Seven patients (23%) experienced grade 3 adverse events, consistent with the known toxicity profile of pembrolizumab; no grade 4 events occurred. To investigate determinants of response, we performed exploratory analyses of longitudinal peripheral blood and paired surgical specimens. Ultrasensitive circulating tumor DNA (ctDNA) profiling showed that post-surgical ctDNA positivity was strongly prognostic and enabled molecular detection of relapse up to 15 months before clinical progression. An XGBoost classifier trained on peripheral immune profiles comprising 231 samples across multiple timepoints from 30 patients demonstrated moderate discriminatory performance for predicting progression (AUROC 0.72), with declines in circulating CD3+ and terminally differentiated effector memory (TDEM) CD8+ T-cell frequencies emerging among the strongest features. Whole-exome sequencing of primary tumors and matched lymph node metastases from six patients revealed unique clonal expansions in metastatic sites. Two patients (33%) remained disease-free and demonstrated lower variant allele frequencies in their lymph nodes compared to their primary disease sites, while four patients (67%) experienced disease recurrence and had an elevated mutational burden in their metastatic sites. Although no convergent clonal evolutionary pattern emerged, we found that copy-number alterations on chromosomes 11, 14, and 19 correlated with clinical outcomes. Notably, deletions involving immunoglobulin heavy chain loci (IGHD, IGHM) were identified in patients with prolonged disease control, suggesting a potential contribution of B-cell–associated immunity in favorably shaping the tumor immune microenvironment. Other lymph node-specific genetic deletions (HCN2, CD177P1, TEX101) were also found to be shared exclusively in patients with durable responses, indicating a favorable role in disease biology and warranting further experimental validation. This study represents the first evaluation of adjuvant PD-1 blockade in HR+ IBC and demonstrates encouraging clinical activity relative to historical expectations. The accompanying biomarker analyses offer initial insight into immune and genomic correlates of outcomes and may help identify patients most likely to benefit from immunotherapy in this aggressive subtype. Citation Format: Ranjan Upadhyay, Angela Alexander, Qing Ye, Ken Chen, John M. Elizarraras, Angela Marx, Megumi Kai, Clinton Yam, Hui Gao, Huiming Sun, Gregory J. Hogan, Siming Zhang, Matthew L. LaBella, Sarah Ratzel, Roland L. Bassett, MDACC Inflammatory Breast Cancer Team, Wendy A. Woodward, Bora Lim. A phase II trial of adjuvant PD-1 blockade with endocrine therapy in hormone receptor positive inflammatory breast cancer: Circulating biomarkers and molecular correlates of clinical outcomes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT172.

Neoadjuvant immunotherapy (nIO) followed by a therapeutic lymph node dissection (TLND) for patients with clinically node-positive melanoma is supported by level 1 evidence. Our aim was to assess the association of pathologic response (PR) and nIO regimen with survival among patients with clinical stage III melanoma undergoing nIO and TLND. Our study included patients treated with nIO followed by a TLND from a large academic institution between 2016 and 2024. The pathologic response was assessed using established guidelines. Differences in extent of PR (PR) by nIO regimen were examined. Disease-free survival (DFS) and overall survival (OS) by PR and nIO regimen were assessed. The study included 121 patients (78.5

Abstract Purpose: Inflammatory breast cancer (IBC) is a rare, highly aggressive subtype marked by rapid proliferation, extensive angio-/lymphangiogenesis, and early metastasis. CCR7, a chemokine receptor involved in immune trafficking, promotes tumor migration toward lymphatics via CCL19/CCL21. This study provides an integrated genomic, protein, spatial, and functional evaluation of CCR7 in IBC to assess its therapeutic potential. Methods: Clinical analysis used genomic data from HR+ HER2- and TNBC IBC compared with subtype-matched non-IBC. CCR7 expression was assessed in IBC and non-IBC cell lines by immunoblotting; ligand secretion (CCL19/CCL21) in tumor and stromal cells was measured by ELISA. CCR7 localization was evaluated using subcellular fractionation and IF, along with testing of a CCR7-blocking antibody. Multiplex IF was performed on BCM PDX models representing distinct CCR7 genomic and protein states. Functional studies included the CCR7 antagonist Navarixin, CCL19/21-induced migration assays, and generation of CCR7 CRISPR knockout clones. Results: CCR7 CNAs occurred in both IBC and non-IBC but did not correlate with mRNA or protein levels. CCR7 protein was broadly expressed, with strongest membranous expression in A3250 and variable levels in IBC-3, SUM-190, and SUM-149. The blocking antibody reduced membranous CCR7 only in A3250, indicating subtype-specific accessibility. IBC cell lines did not secrete CCL19/CCL21, supporting reliance on stromal ligands, which varied by coculture. Across six BCM PDXs, CCR7 was consistently expressed, whereas ligand levels were heterogeneous; MBI-117 showed high CCL19/CCL21. Spatial profiling revealed CCR7+ tumor cells aligned along Podoplanin+ lymphatics with CCL21+ stromal cells and CD163+ macrophages enriched around CCR7+ emboli. Navarixin reduced proliferation in IBC3 and SUM-190 by 96h, and CCL19/21 enhanced migration in A3250 and SUM-149. CCR7-KO SUM-149 clones were generated, with functional analyses ongoing. Conclusion: CCR7 expression in IBC is independent of copy number and supported by a ligand-rich microenvironment that positions CCR7+ tumor cells along lymphatics. Integrated genomic, spatial, and functional data support CCR7 as a therapeutic target in IBC, with studies ongoing. Citation Format: Surbhi Shivhare, Caren Sanchez, Richard Larson, Lacey Dobrolecki, Michael Lewis, Jennifer Chen, Susanne Lin, Anastasiya Evdokimova, Daria Goncharova, Angela Alexander, Azadeh Nasrazadani, Rachel Layman, Bora Lim, Vicente Valero, Anthony Lucci, The MDACC Inflammatory Breast Cancer Team, Wendy A. Woodward. CCR7 expression and spatial distribution in inflammatory breast cancer: A baseline characterization for therapeutic targeting [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3763.

Table S2 demonstrates multivariable Cox proportional hazards model, excluding patients who were pregnant at time of diagnosis

BACKGROUND:Studies regarding therapeutic response of invasive lobular carcinoma (ILC) to neoadjuvant systemic therapy (NST) suggest that ILC is less favorable and the prognostic impact of a pathologic complete response (pCR) is unclear. PATIENTS AND METHODS:This study included 853 (NAC; n = 715 and NET; n = 138) non-metastatic classic ILC cases that received NST followed by surgery. Propensity-score matched analysis (PSMA) was performed to compare clinicopathologic groups. Survival outcomes were compared for patients with and without a pCR. RESULTS:Most had large primary tumors with nodal metastases (89.5% cT2-T4, 64% cN+) and luminal subtype tumors (87.6%). Patients receiving NAC were more likely to be clinically node-positive (69.1% versus 34.3%; p = 0.0005), have grade 3 disease (18.7% versus 8.7%; p = 0.0082), and undergo mastectomy (84.2% versus 69.6%; p < 0.001) and ALND (84.9% versus 57.3%; p < 0.0001) compared with NET. Overall, breast and axillary nodal pCR rates were 4.9% and 9.3%, respectively. Among 155 patients who had SLNB, there was 1 axillary nodal recurrence (0.6%). The 10-year distant recurrence-free survival (DRFS) for patients with a breast pCR was 61% versus 46% for those without (p = 0.267). Patients with a nodal pCR demonstrated higher 10-year DRFS (49% versus 33%; p = 0.026) and OS compared with those without (65% versus 48%; p = 0.068). No survival outcome difference was seen for patients treated with NAC versus NET on PSMA. CONCLUSIONS:Nodal pCR was associated with survival outcomes in ILC and systemic therapy decision-making should be reconsidered. SLNB after NST appears to be safe and effective in ILC.

AbstractBackground: Postpartum diagnosis of breast cancer confers increased risk of metastasis and death, possibly because of protumorigenic pathways that occur after weaning. We sought to evaluate the impact of postpartum diagnosis on survival in patients with inflammatory breast cancer (IBC). Methods: We performed a retrospective analysis of patients with nonmetastatic IBC enrolled in a prospective registry (2007–2023). Kruskal–Wallis, χ2, and Fisher exact tests were used to compare between postpartum groups. The Kaplan–Meier method and log-rank tests were used for survival estimates. Results: Among 320 patients with IBC, 25 (7.8%) were nulliparous, 31 (9.7%) were 0 to 5 years postpartum, 26 (8.1%) were 6 to 10 years postpartum, 56 (17.5%) were 11 to 20 years postpartum, and 182 (56.9%) were >20 years postpartum. Groups were similar with respect to race/ethnicity, body mass index, grade, receptor subtype, stage, trimodality therapy receipt, and pathologic complete response rate. At a median follow-up of 77 months (95% confidence interval, 69.3–86.5), there were no significant differences in overall survival, progression-free survival, and locoregional and distant recurrence-free survival by postpartum status. On multivariable analysis, parity status and years postpartum were not significantly associated with survival outcomes after controlling for age, stage, and receptor subtype. Conclusions: In this cohort of patients with IBC with a high proportion of childbearing, postpartum diagnosis did not significantly affect survival outcomes. The aggressive biology of IBC may override any additional risks imposed by a postpartum diagnosis. Impact: Unlike in noninflammatory invasive breast cancer, postpartum diagnosis did not negatively affect prognosis in IBC. These findings highlight the continuing need to identify unique drivers of aggressive biology in IBC.

A crucial adaptability trait of stem-like melanoma cells that persist under all selection pressures, including therapies, is their ability to survive in deep quiescence. This ability coupled with their intrinsic ability to proliferate leads to recurrence. Here we describe an approach to modeling this trait in cell culture. A lack of glutamine proved to be a selection pressure for the highly metastatic human melanoma cell line A375SM, killing more than 99% of cells and selecting rare cells based on their ability to survive in deep quiescence. After 4 weeks, cells gradually exited quiescence and proliferated indefinitely. Interestingly, by not providing fresh glutamine-free medium at this stage, we could select rare cells that persist in deep quiescence as single cells. Alternatively, we could model deeper quiescence lasting longer than 4 weeks by increasing the severity of the selection pressure using dialyzed serum in medium. The cells selected in this manner were much more resistant to paclitaxel than was their parental cell line. We obtained similar results with the highly metastatic mouse melanoma cell line B16-BL6. Thus, our phenotype-based approach is suitable for modeling abnormal deep quiescence in melanoma that is responsible for therapy resistance, disease progression, and recurrence/metastasis.

e12594 Background: Patients with Stage III triple negative (TN) inflammatory breast cancer (IBC) are treated based on standard-of-care practices inclusive of the Keynote 522 regimen (KN522). Outcomes, however, are inferior to what has been reported in the non-IBC setting. Patients achieving pathologic complete response (pCR) were compared to those not achieving pCR in a cohort of patients with IBC receiving KN522 to evaluate for predictors of response. Methods: RNA sequencing (RNA-seq) was performed on 26 samples from 23 patients with IBC undergoing KN522 in the neoadjuvant setting (N = 19 baseline pre-treatment, N = 7 surgical post treatment, N = 5 paired samples). BostonGene’s Breast Cancer Classifier (BCC) was utilized to determine intrinsic subtypes. Tumor microenvironment was determined by BostonGene’s Tumor Portrait assay. Results: Among patients achieving pCR in the studied cohort (N = 4), 75% (N = 3) and 25% (N = 1) patients had basal and luminal B subtype, respectively, while in the non-pCR group (N = 5), 30% (N = 3) were HER2-low. The pCR group demonstrated higher PD-L1 RNA-seq expression and a trend towards higher abundance of T cell subsets in the tumor cell microenvironment comparatively. Among non-pCR cases, deconvolution analysis revealed reduced tumor fractions following neoadjuvant systemic therapy. A shift in tumor portrait was observed in 3/5 samples, including increased fibrosis features in two cases and loss of immune component in one. These non-pCR cases showed increased angiogenesis and endothelial enrichment signatures, trending toward reduced matrix remodeling. No association was identified between immune-related adverse events (irAEs) and either pCR or BCC subtype. Conclusions: While the small sample size and molecular heterogeneity preclude our ability to draw definitive conclusions, our findings show that in TN IBC, response to neoadjuvant therapy correlated with high PD-L1 expression and T cell abundance, whereas non-responders demonstrated angiogenic and endothelial shifts. No association was observed between irAEs and pCR or BCC. These findings highlight potential biomarkers of response and progression in TN IBC; however, interpretation is limited by the small cohort size and molecular heterogeneity.

Abstract Background: Circulating immune profiles offer a noninvasive approach to monitor treatment response in breast cancer. Inflammatory breast cancer (IBC), although clinically distinct, shares resistance and immune evasion features among each other. To identify immune escape mechanisms and early predictors of response in IBC, we profiled longitudinal peripheral immune markers and evaluated their association with pathologic complete response (pCR) and residual cancer burden (RCB) across treatment regimens and subtypes and developed composite immune indices to improve prediction under class imbalance. Methods: Peripheral blood samples (n=93) from patients treated with neoadjuvant or induction therapy for IBC were analyzed by multiparameter flow cytometry and annotated for subtype, regimen, pCR, and RCB. Group comparisons used Mann-Whitney U (pCR) and Kruskal-Wallis (RCB). Predictive models included logistic regression and random forest classifiers with class-weighting. Composite indices included CD8 Exhaustion, CD8 Memory, NK-ADCC scores derived from z-scaled components. Model performance was assessed using 5-fold cross-validation with AUC, PR-AUC, and calibration. Planned extensions include leave-one-regimen validation, temporal analyses, and external evaluation using a pre-registered pipeline. Results: Univariate analyses identified significant associations between pCR and the CD8 Exhaustion Index (p≈0.007) and CD8 Memory Index (p≈0.038), with NK-ADCC trending (p≈ 0.078). Logistic regression and random forest models incorporating combined indices improved AUC from ∼0.70 when individually associated, to ∼0.92 ± 0.07 (5-fold CV), albeit with wide uncertainty due to only up to 5 pCR events. Individual markers linked to pCR included Stem_Memory_CD8, NKG2A_ADCC, and CTLA4_CD8, while CD56hi NK and NKG2A +CD56hi NK distinguished RCB gradients (p<0.05 before correction). No markers remained significant after FDR adjustment given sample size. Conclusions: Peripheral immune signatures, particularly combined CD8 exhaustion, memory indices, NK ADCC were associate with higher pCR and lower RCB. Composite indices outperform single markers and capture the balance between immune activation and suppression. Ongoing cross-cohort validation will assess generalizability across regimens and subtypes. Severe class imbalance (∼5/93 pCR) and small subgroup sizes constrain precision of our analysis. Findings are hypothesis-generating and warrant external validation in larger prospective cohorts. Citation Format: Hui Gao, Ranjan Upadhyay, Angela Alexander, Angela N. Marx, Megumi Kai, Chelain R. Goodman, Azadeh Nasrazadani, Savitri Krishnamurthy, Anthony Lucci, Rachel M. Layman, Sadia Saleem, Vicente Valero, Michael C. Stauder, Susie X. Sun, Gary J. Whitman, Miral M. Patel, Huong C. Le-Petross, Chasity L. Yajima, Lily Villarreal, Heather Lopez, Bora Lim. Peripheral immune indices predict pathologic complete response and residual cancer burden in inflammatory breast cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3744.

Abstract Cancer is an evolution like process; wherein genetically abnormal cells persist despite a variety of mechanisms designed to kill such cells. Immune checkpoint and targeted therapies have significantly improved outcomes in melanoma. However, residual disease remaining after treatment, as indicated by a lack of complete pathological response or as detected by other sensitive methods, often evolves further leading to recurrence/metastasis. Thus, there is a need to inhibit or eradicate residual disease to prevent recurrence. In this regard, there is a lack of good preclinical models of residual disease, particularly for testing new therapies that would inhibit quiescent or slow-growing melanoma cells. This is important since opportunistically switching to quiescence and to survive in deep quiescence are major hurdles in improving outcomes. Our approach to a cell culture model of residual disease aligns with the idea that selection pressures are important in enforcing cancer cell quiescence. A selection pressure involving a severe and extended metabolic change, such as a lack of glutamine in culture medium, is an excellent choice for eliminating bulk of sensitive cells that proliferate in artificially rich medium. We subjected two highly metastatic melanoma cell lines, A375SM (representing undifferentiated melanoma with a common BRAF V600E mutation and homozygous CDKN2A deletion) and B16-BL6 (suitable for syngeneic mouse model), to glutamine deficiency in two ways: 1) culture in Gln-free medium (with low 27 µM Gln coming from serum, instead of 4 mM Gln in complete medium), and 2) culture in stringent Gln-free medium (near zero Gln with the use of dialyzed serum in medium). More than 99% cells died in Gln-free medium; rare cells survived in deep quiescence, and then gradually exited quiescence after 4-5 weeks and proliferated indefinitely. We extended the quiescence to 7 weeks and beyond by culturing A375SM cells in stringent Gln-free medium. In these experiments, we replaced medium with fresh medium every 2-3 weeks. Interestingly, if we did not replace medium for an extended period (50 days), we found that A375SM cells did not exit quiescence. We interpret that rare cells surviving in deep quiescence gradually develop an ability to exit quiescence; however, this exit or/and proliferation requires some glutamine. By not changing medium for an extended period, low level of Gln got exhausted, and cells stayed quiescent. We refer to the cells selected in this manner as metabolically adaptable (MA); they are broadly adaptable. The MA cells were much more resistant to paclitaxel than were their parental cell lines. Our results support the feasibility of the approach for modeling residual disease. In conclusion, when we approach deep intrinsic resistance in melanoma with a new perspective (abnormal quiescence besides abnormal proliferation leading to recurrence), new insights and fresh solutions are likely to emerge. Citation Format: Balraj Singh, Vanessa N. Sarli, Nikil Erry, Anthony Lucci. Residual disease on a dish: A practical approach to deep intrinsic resistance in melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7438.

BACKGROUND:Inflammatory Breast Cancer (IBC) is an aggressive breast cancer with poor prognosis. Nodal staging with ultrasound (US) and 18F-FDG PET/CT (FDG PET/CT) is accurate and beneficial for determining locoregional treatment. The aim of this study is to determine if the nodal disease distribution at initial presentation on US and FDG PET/CT can predict overall survival (OS). METHODS:Nodal features of patients with IBC from an Institutional Review Board approved registry, who received both US and FDG PET/CT, were retrospectively analyzed. Kaplan-Meier method and Cox regression were used to evaluate the association of nodal distribution predictors with overall survival, and the exact McNemar test to compare nodal distribution between US and FDG PET/CT. RESULTS:Of 188 IBC patients, US detected malignant ipsilateral adenopathy in 55.9%, 33.5%, and 19.7% at axillary levels I, II, and III respectively, and FDG PET/CT in 51.6%, 29.3%, and 14.9%. FDG PET/CT detected supraclavicular lymphadenopathy (SC) in 20.7%. No statistically significant difference was found between US and FDG PET/CT for detection of ipsilateral nodal disease. Median OS was 3.99 years (95% CI, 3.38-6.35 years). Worse prognosis was associated with contralateral SC (HR 4.05, P < .001) on FDG PET/CT, compared to ipsilateral SC (HR 1.93, P = .003) and ipsilateral axillary adenopathy (HR range, 1.16-1.87). CONCLUSION:IBC patients with initial presentation of contralateral SC have significantly reduced OS by approximately 3 years. No statistically significant difference was noted between US or FDG PET/CT for ipsilateral locoregional staging in IBC. US performed by experienced operators showed detection rates comparable to FDG PET/CT. FDG PET/CT remains crucial for detecting distant metastases.

Table S1 demonstrates OS, PFS, and RFS by receptor subtype

Inflammatory breast cancer (IBC) is a rare yet highly aggressive subtype of breast cancer, characterized by distinct clinical features, rapid progression, and complex biology. Despite decades of research, patient outcomes remain poor, underscoring the need for innovative approaches. The International IBC Symposium 2025 convened global experts to discuss advances in the field and to outline strategic priorities for research and clinical care. This report summarizes the key themes discussed. A major topic was IBC biology, with particular emphasis on tumor emboli formation and tumor microenvironment interactions, which shape the distinctive characteristics of the disease. Updates in molecular and immune profiling were presented, illustrating how these data may guide personalized therapeutic approaches. From a therapeutic standpoint, the importance of trimodal therapy in patients with nonmetastatic IBC was reinforced, while highlighting the need to investigate novel agents, rational drug combinations, and biologically informed strategies to improve outcomes. Additional sessions addressed optimization of locoregional management, even for selected patients with metastatic disease. Experts also discussed emerging technologies, including spatial transcriptomics, artificial intelligence tools, and liquid biopsy, as promising methods to advance disease characterization, facilitate earlier detection, and refine disease monitoring. Finally, a common theme across presentations was the critical importance of expanding awareness and education, as well as fostering global collaboration through the IBC International Consortium to standardize diagnosis, accelerate translational research, and ensure equitable access to care. Collectively, these efforts aim to redefine the clinical trajectory of IBC and move the field closer to achieving durable disease control and, ultimately, curative outcomes.

614 Background: Optimal outcomes in Inflammatory Breast Cancer (IBC) are achieved with trimodal therapy. We sought to evaluate how differences in response to neoadjuvant chemotherapy (NAC) in the breast and axilla impact locoregional recurrence-free, distant recurrence-free and overall survival in patients with IBC. Methods: A retrospective analysis was performed on patients with IBC enrolled in a prospective registry from 2007-2025. All patients underwent NAC followed by modified radical mastectomy. Comparisons between three pathologic response groups—(A) pCR, no residual disease in breast or lymph nodes, (B) complete response in breast but not axillary nodes, and (C) complete response in axillary nodes, but not breast—were performed using Kaplan-Meier and pairwise Cox proportional hazards models. Results: 545 patients were included; median age was 50 (IQR:41-58). pCR was identified in 150 (28%) patients, while 34 (6%) were in group B, and 55 (10%) were in group C. Of patients with pCR, 6 (4%) had locoregional recurrence (LRR), compared to 6 (17%) of patients in group B, 5 (9%) of patients in group C, and 79 (25%) in patients without pCR. There was decreased risk of LRR in patients with pCR compared to no pCR, or group B (HR:0.118 CI 0.05-0.27 P<0.001; HR:0.18 CI 0.06-0.55 P=0.017). A similar decreased risk of LRR was observed in patients with group C compared to no pCR (HR:0.297 CI 0.12-0.73 P=0.01). Of patients with pCR, 31 (20%) had distant recurrence, compared to 14 (41%) of patients in group B, 23 (41%) of patients in group C, and 183 (60%) in patients who did not have pCR. There was decreased risk of distant recurrence in patients with pCR compared to no pCR, or patients in group C (HR0.25 CI 0.17-0.37 P<0.0001; HR0.43 CI0.25-0.74 P=0.007). There was also a decreased risk of distant recurrence in patients with group C compared to no pCR (HR0.59 CI 0.38-0.91 P=0.027). Mean OS was longer in patients with pCR compared to partial response or no pCR (12.4 vs 7.95 years). The risk of death was lower in patients with pCR compared to partial or no pCR, as well as those with group C compared to no pCR. Conclusions: In patients with IBC, the lowest risk for recurrence was achieved with pCR. However, even with pCR, there was still a 20% chance of distant recurrence. Partial response through clearance of the lymph node disease provided some reduction in risk of recurrence compared to no pCR.

Figure S1 demonstrates survival outcomes for the overall study cohort, broken down by overall survival (OS), progression-free survival (PFS), locoregional recurrence-free survival (RFS), and distant RFS.

Selecting treatments for triple-negative breast cancer (TNBC) remains challenging due to its high molecular and phenotypic heterogeneity. To maximize response rates, nearly all patients are treated with an aggressive combination of chemo-immunotherapy. However, since half of patients respond to chemotherapy alone and about a third do not respond at all, the majority of patients would benefit from alternative regimens. Thus, there is a pressing need to better personalize or de-escalate therapy using response-based biomarkers. To address this need, we conducted the ARTEMIS randomized trial (NCT 02276443) to test whether a molecular classifier could predict response to treatment with neoadjuvant chemotherapy alone in early-stage TNBC, and to understand the correlates of response. This study found that integrating a molecular classifier did not result in a statistically significant improvement in responses to doxorubicin and cyclophosphamide (AC), which increased from 33

Guideline-concordant locoregional therapy (LRT) for inflammatory breast cancer (IBC) consists of modified radical mastectomy (MRM) after neoadjuvant systemic therapy and post-mastectomy radiotherapy (PMRT). Despite advances in systemic therapy, de-escalation of LRT remains unsupported. This review synthesizes modern data affirming guideline-concordant LRT to optimize locoregional control and survival. Utilization of the validated IBC Scoring System can facilitate prompt and accurate diagnosis, yet adherence to life-saving guideline-concordant care is declining. Optimal LRT consists of MRM with resection of involved skin and PMRT delivering an equivalent dose in 2 Gy (Gy) fractions (EQD2) ≥ 60 Gy to the chest wall and involved, unresected lymph nodes. Adherence to guideline-concordant LRT combined with modern systemic therapies is associated with improved survival. With earlier diagnosis and more effective systemic treatments, the potential for LRT to achieve durable remission is amplified. Guideline-concordant LRT remains essential to eradicate locoregional disease and maximize the curative potential of trimodality therapy.